Faculty Bibliography

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic (iEEG) electrodes prior to resective surgery for drug- resistant epilepsy. The current gold standard, electrocortical stimulation mapping (ESM), is time -consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping (STFM) has recently emerged as a potential alternative to ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials (CCEPs) elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone (71.8%), indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice.

OBJECTIVE:The combined spatiotemporal dynamics underlying sign language production remains largely unknown. To investigate these dynamics as compared to speech production we utilized intracranial electrocorticography during a battery of language tasks. METHODS:We report a unique case of direct cortical surface recordings obtained from a neurosurgical patient with intact hearing and bilingual in English and American Sign Language. We designed a battery of cognitive tasks to capture multiple modalities of language processing and production. RESULTS:We identified two spatially distinct cortical networks: ventral for speech and dorsal for sign production. Sign production recruited peri-rolandic, parietal and posterior temporal regions, while speech production recruited frontal, peri-sylvian and peri-rolandic regions. Electrical cortical stimulation confirmed this spatial segregation, identifying mouth areas for speech production and limb areas for sign production. The temporal dynamics revealed superior parietal cortex activity immediately before sign production, suggesting its role in planning and producing sign language. CONCLUSIONS:Our findings reveal a distinct network for sign language and detail the temporal propagation supporting sign production.

Cognitive functions, for example speech processing, are distributed asymmetrically in the two hemispheres that mostly have homologous anatomical structures. Dichotic listening is a well-established paradigm to investigate hemispherical lateralization of speech. However, the mixed results of dichotic listening, especially when using tonal languages as stimuli, complicates the investigation of functional lateralization. We hypothesized that the inconsistent results in dichotic listening are due to an interaction in processing a mixture of acoustic and linguistic attributes that are differentially processed over the two hemispheres. In this study, a within-subject dichotic listening paradigm was designed, in which different levels of speech and linguistic information was incrementally included in different conditions that required the same tone identification task. A left ear advantage (LEA), in contrast with the commonly found right ear advantage (REA) in dichotic listening, was observed in the hummed tones condition, where only the slow frequency modulation of tones was included. However, when phonemic and lexical information was added in simple vowel tone conditions, the LEA became unstable. Furthermore, ear preference became balanced when phonological and lexical-semantic attributes were included in the consonant-vowel (CV), pseudo-word, and word conditions. Compared with the existing REA results that use complex vowel word tones, a complete pattern emerged gradually shifting from LEA to REA. These results support the hypothesis that an acoustic analysis of suprasegmental information of tones is preferably processed in the right hemisphere, but is influenced by phonological and lexical semantic processes residing in the left hemisphere. The ear preference in dichotic listening depends on the levels of speech and linguistic analysis and preferentially lateralizes across the different hemispheres. That is, the manifestation of functional lateralization depends on the integration of information across the two hemispheres.

Dynamic interactions between remote but functionally specialized brain regions enable complex information processing. This intercortical communication is disrupted in the neural networks of patients with focal epilepsy, and epileptic activity can exert widespread effects within the brain. Using large-scale human intracranial electroencephalography recordings, we show that interictal epileptiform discharges (IEDs) are significantly coupled with spindles in discrete, individualized brain regions outside of the epileptic network. We found that a substantial proportion of these localized spindles travel across the cortical surface. Brain regions that participate in this IED-driven oscillatory coupling express spindles that have a broader spatial extent and higher tendency to propagate than spindles occurring in uncoupled regions. These altered spatiotemporal oscillatory properties identify areas that are shaped by epileptic activity independent of IED or seizure detection. Our findings suggest that IED-spindle coupling may be an important mechanism of interictal global network dysfunction that could be targeted to prevent disruption of normal neural activity.

The principles underlying functional asymmetries in cortex remain debated. For example, it is accepted that speech is processed bilaterally in auditory cortex, but a left hemisphere dominance emerges when the input is interpreted linguistically. The mechanisms, however, are contested, such as what sound features or processing principles underlie laterality. Recent findings across species (humans, canines and bats) provide converging evidence that spectrotemporal sound features drive asymmetrical responses. Typically, accounts invoke models wherein the hemispheres differ in time-frequency resolution or integration window size. We develop a framework that builds on and unifies prevailing models, using spectrotemporal modulation space. Using signal processing techniques motivated by neural responses, we test this approach, employing behavioural and neurophysiological measures. We show how psychophysical judgements align with spectrotemporal modulations and then characterize the neural sensitivities to temporal and spectral modulations. We demonstrate differential contributions from both hemispheres, with a left lateralization for temporal modulations and a weaker right lateralization for spectral modulations. We argue that representations in the modulation domain provide a more mechanistic basis to account for lateralization in auditory cortex.

Direct recordings from the human brain have historically involved epilepsy patients undergoing invasive electroencephalography (iEEG) for surgery. However, these measurements are temporally limited and affected by clinical variables. The RNS System (NeuroPace, Inc.) is a chronic, closed-loop electrographic seizure detection and stimulation system. When adapted by investigators for research, it facilitates cognitive testing in a controlled ambulatory setting, with measurements collected over months to years. We utilized an associative learning paradigm in 5 patients with traditional iEEG and 3 patients with chronic iEEG, and found increased hippocampal gamma (60-100 Hz) sustained at 1.3-1.5 seconds during encoding in successful versus failed trials in surgical patients, with similar results in our RNS System patients (1.4-1.6 seconds). Our findings replicate other studies demonstrating that sustained hippocampal gamma supports encoding. Importantly, we have validated the RNS System to make sensitive measurements of hippocampal dynamics during cognitive tasks in a chronic ambulatory research setting.